ClinVar Miner

Submissions for variant NM_022124.6(CDH23):c.2104C>T (p.Arg702Trp)

gnomAD frequency: 0.00001  dbSNP: rs528779319
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000155952 SCV000205664 uncertain significance not specified 2013-08-15 criteria provided, single submitter clinical testing The Arg702Trp variant in CDH23 has not been reported in individuals with hearing loss or in large population studies. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg702Trp variant may impact the protein, though this information is not predict ive enough to determine pathogenicity. In summary, additional information is nee ded to fully assess the clinical significance of the Arg702Trp variant.
GeneDx RCV001731486 SCV001982132 uncertain significance not provided 2021-10-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001731486 SCV003513526 uncertain significance not provided 2021-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 702 of the CDH23 protein (p.Arg702Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs528779319, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with CDH23-related conditions. ClinVar contains an entry for this variant (Variation ID: 179166). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C65"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001275934 SCV001461614 uncertain significance Usher syndrome type 1 2020-04-15 no assertion criteria provided clinical testing

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